Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients

Yu Shun Lin; Yen Chu Chen; Tzu En Chen; Mei Ling Cheng; Ke Shiuan Lynn; Pramod Shah; Jin Shing Chen; Rwei Fen S. Huang

doi:10.3390/nu15010003

Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients

Yu Shun Lin, Yen Chu Chen, Tzu En Chen, Mei Ling Cheng, Ke Shiuan Lynn, Pramod Shah, Jin Shing Chen^*, Rwei Fen S. Huang^*

^*Corresponding author for this work

Department of Biomedical Sciences (Master's Program in Clinical Trials Assessment)

Research output: Contribution to journal › Journal Article › peer-review

6 Scopus citations

Abstract

Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58–0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (GLUT1), de no serine synthesis (PHGDH, PSPH, and PSAT1), folate cycle (SHMT1/2 and PCFR), and down-regulation in glutaminolysis (SLC1A5, SLC7A5, GLS, and GLUD1). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.

Original language	English
Article number	3
Journal	Nutrients
Volume	15
Issue number	1
DOIs	https://doi.org/10.3390/nu15010003
State	Published - 20 12 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

WGCNA
non–small-cell lung cancers
target metabolomics
transcriptional profile
tumour folate
Folic Acid
Prognosis
Minor Histocompatibility Antigens
Humans
Amino Acid Transport System ASC
Carcinoma, Non-Small-Cell Lung/metabolism
Glutamine/metabolism
Tandem Mass Spectrometry
Lung Neoplasms/metabolism
Metabolomics/methods

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/nu15010003

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title = "Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients",

abstract = "Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58–0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (GLUT1), de no serine synthesis (PHGDH, PSPH, and PSAT1), folate cycle (SHMT1/2 and PCFR), and down-regulation in glutaminolysis (SLC1A5, SLC7A5, GLS, and GLUD1). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.",

keywords = "WGCNA, non–small-cell lung cancers, target metabolomics, transcriptional profile, tumour folate, Folic Acid, Prognosis, Minor Histocompatibility Antigens, Humans, Amino Acid Transport System ASC, Carcinoma, Non-Small-Cell Lung/metabolism, Glutamine/metabolism, Tandem Mass Spectrometry, Lung Neoplasms/metabolism, Metabolomics/methods",

author = "Lin, \{Yu Shun\} and Chen, \{Yen Chu\} and Chen, \{Tzu En\} and Cheng, \{Mei Ling\} and Lynn, \{Ke Shiuan\} and Pramod Shah and Chen, \{Jin Shing\} and Huang, \{Rwei Fen S.\}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = dec,

day = "20",

doi = "10.3390/nu15010003",

language = "英语",

volume = "15",

journal = "Nutrients",

issn = "2072-6643",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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TY - JOUR

T1 - Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients

AU - Lin, Yu Shun

AU - Chen, Yen Chu

AU - Chen, Tzu En

AU - Cheng, Mei Ling

AU - Lynn, Ke Shiuan

AU - Shah, Pramod

AU - Chen, Jin Shing

AU - Huang, Rwei Fen S.

PY - 2022/12/20

Y1 - 2022/12/20

N2 - Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58–0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (GLUT1), de no serine synthesis (PHGDH, PSPH, and PSAT1), folate cycle (SHMT1/2 and PCFR), and down-regulation in glutaminolysis (SLC1A5, SLC7A5, GLS, and GLUD1). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.

AB - Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58–0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (GLUT1), de no serine synthesis (PHGDH, PSPH, and PSAT1), folate cycle (SHMT1/2 and PCFR), and down-regulation in glutaminolysis (SLC1A5, SLC7A5, GLS, and GLUD1). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.

KW - WGCNA

KW - non–small-cell lung cancers

KW - target metabolomics

KW - transcriptional profile

KW - tumour folate

KW - Folic Acid

KW - Prognosis

KW - Minor Histocompatibility Antigens

KW - Humans

KW - Amino Acid Transport System ASC

KW - Carcinoma, Non-Small-Cell Lung/metabolism

KW - Glutamine/metabolism

KW - Tandem Mass Spectrometry

KW - Lung Neoplasms/metabolism

KW - Metabolomics/methods

UR - https://www.scopus.com/pages/publications/85145934396

U2 - 10.3390/nu15010003

DO - 10.3390/nu15010003

M3 - 文章

C2 - 36615660

AN - SCOPUS:85145934396

SN - 2072-6643

VL - 15

JO - Nutrients

JF - Nutrients

IS - 1

M1 - 3

ER -

Probing Folate-Responsive and Stage-Sensitive Metabolomics and Transcriptional Co-Expression Network Markers to Predict Prognosis of Non-Small Cell Lung Cancer Patients

Abstract

Bibliographical note

Keywords

UN SDGs

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